Peripheral Neuronal Mechanisms of Itch

瘙痒伴随着许多神经、皮肤科和全身疾病，并导致痛苦和损失 生活质量。人类这种感觉背后的外周神经机制仍然很差。 明白了。我们建议的总体目标是确定急性瘙痒和长期瘙痒 瘙痒疾病编码在皮肤伤害性感受器的放电中。我们建议电生理学 非人灵长类动物对瘙痒化学刺激反应的实验研究 人类外周伤害性神经纤维及其相关的补充心理物理研究 确定这些不同的神经元群体在瘙痒感觉中的作用。我们将测试以下预测 该模型认为，皮肤伤害性感受器通过以下两种方式分别发出瘙痒和痛觉刺激的信号 被激活的传入的总数或其放电的速率或模式。在临床上相关的 即SADBE变态反应性接触性皮炎模型，我们将研究 化学和热刺激引起的自发性瘙痒和增强瘙痒的神经机制 人类的心理物理学研究和猴子伤害性传入的电生理记录。 通过研究急性和长期瘙痒，我们将第一次能够识别发生在 周围神经系统处于临床相关的瘙痒状态。更好地了解伤害性感受器如何 调节正常皮肤和瘙痒皮肤的瘙痒感觉将增加发展和 评估新的外周作用药物，这些药物可以降低慢性阻塞性肺疾病潜在的异常伤害性感受器功能 很痒。

Itch accompanies many neurological, dermatological and systemic diseases and leads to suffering and loss in the quality of life. The peripheral neuronal mechanisms underlying this sensation in human are still poorly understood. The overall goal of our proposal is to determine how acute itch and the prolonged itch from a pruritic disease are encoded in the discharges of cutaneous nociceptors. We propose electrophysiological experiments in nonhuman primate to characterize the responses to pruritic chemical stimuli in subtypes of peripheral nociceptive nerve fibers and complementary, correlative psychophysical studies in human to determine the role of these different neuronal populations in itch sensation. We will test the predictions of models that propose that cutaneous nociceptors differentially signal pruritic and algesic stimuli either by the overall number of afferents activated or by the rates or patterns of their discharges. In a clinically relevant model of prolonged itch, namely the SADBE model of allergic contact dermatitis, we will investigate the neuronal mechanisms of spontaneous itch and enhanced itch to chemical and heat stimuli using psychophysical studies in humans and electrophysiological recordings from nociceptive afferents in monkeys. By studying both acute and prolonged itch, we will be able to identify, for the first time, changes that occur in the peripheral nervous system in a clinically relevant itch condition. A better understanding of how nociceptors mediate the sensation of itch in normal and pruritic skin will increase the possibility of developing and evaluating novel, peripherally acting drugs that reduce the abnormal nociceptor function underlying chronic itch.